WO2024007583A1 - Utilisation de ginsénoside en combinaison avec un bloqueur de pd-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou - Google Patents

Utilisation de ginsénoside en combinaison avec un bloqueur de pd-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou Download PDF

Info

Publication number
WO2024007583A1
WO2024007583A1 PCT/CN2023/075142 CN2023075142W WO2024007583A1 WO 2024007583 A1 WO2024007583 A1 WO 2024007583A1 CN 2023075142 W CN2023075142 W CN 2023075142W WO 2024007583 A1 WO2024007583 A1 WO 2024007583A1
Authority
WO
WIPO (PCT)
Prior art keywords
ginsenoside
cell carcinoma
squamous cell
neck squamous
head
Prior art date
Application number
PCT/CN2023/075142
Other languages
English (en)
Chinese (zh)
Inventor
孙晓波
邢小燕
强伟杰
Original Assignee
中国医学科学院药用植物研究所
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 中国医学科学院药用植物研究所 filed Critical 中国医学科学院药用植物研究所
Publication of WO2024007583A1 publication Critical patent/WO2024007583A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • This application belongs to the field of head and neck squamous cell carcinoma treatment in the field of medical technology. Specifically, this application provides the use of ginsenoside Rh2 or Rg3 combined with a PD-1 blocker in the preparation of drugs for the treatment of head and neck squamous cell carcinoma.
  • Head and neck squamous cell carcinoma (referred to as head and neck squamous cell carcinoma) is one of the most common malignant tumors in the world. There are more than 650,000 new cases and 330,000 deaths every year, which are characterized by high mortality and easy recurrence; see Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin. 2018;68:394-424. This is a highly invasive heterologous disease with special anatomical locations and complex types, which seriously affects the patient's appearance, chewing, smell and other basic physiological functions and quality of life.
  • Immunotherapy is a treatment method that promotes the immune system to recognize and eliminate tumor cells by restoring the body's normal immune response. It is considered to be the most promising method for treating advanced or aggressive cancers.
  • PD-1 is the most widely studied and used method.
  • Blockers Although immunotherapy can significantly improve the treatment effect of patients with head and neck squamous cell carcinoma, the objective response rate is only about 20%, and only a small number of patients can benefit from it. Studies have shown that combined immunotherapy can significantly improve the tumor response rate and reduce the risk of disease progression, thereby prolonging overall survival and improving patients' quality of life.
  • common combination immunotherapy options include: PD-1 blockers combined with chemotherapy, PD-1 blockers combined with radiotherapy, PD-1 blockers combined with targeted drugs, PD-1 blockers combined with other immunotherapy Therapy combination.
  • Ginseng is the dried root of Panax ginseng, a plant in the Araliaceae family. It is a representative traditional Chinese medicine with immune-regulating effects. It has the functions of tonifying vitality, rejuvenating pulse and fixing prolapse, nourishing the spleen and lungs, producing body fluids and calming the nerves.
  • ginsenosides As the main active ingredient in ginseng, ginsenosides have been widely studied for their anti-tumor and immune modulation effects. Ginsenosides can undergo metabolic transformation in the body, and their anticancer activity and bioavailability are increased.
  • Ginsenoside Rh2 is the main metabolite of Rg3, with its oral bioavailability increased by 5 times and its content increased by 50 times; see Yang, L., Zou, H., Gao, Y., Luo, J., Xie, X.,Meng,W.,Zhou,H.,&Tan,Z.(2020).Insights into gastrointestinal microbiota-generated ginsenoside metabolites and their bioactivities.Drug metabolism reviews,52(1),125–138; Zhao C,Sun R,Cao B,et al.An in vitro metabolic system of gut flora and the metabolism of ginsenoside Rg3 and cholic acid.Eur J Drug Metab Pharmacokinet.2014;39(2):129-137. Ginsenosides Rg3 and Rh2 are considered to be valuable for further development and utilization, and have the potential to enhance the anti-tumor efficacy of immunotherapy.
  • this application researches and develops a plan for the combined use of ginsenosides and PD-1 blockers in the treatment of head and neck squamous cell carcinoma to give full play to the synergistic effect of the drugs.
  • the attenuated effect provides a safer and more effective drug combination and usage method for the clinical treatment of head and neck squamous cell carcinoma.
  • this application provides the use of ginsenosides combined with PD-1 blockers in the preparation of anti-head and neck squamous cell carcinoma drugs.
  • the present application provides the use of ginsenosides in the preparation of synergists that enhance the treatment of head and neck squamous cell carcinoma with PD-1 blockers.
  • the present application provides a pharmaceutical composition for treating head and neck squamous cell carcinoma, which contains ginsenoside and PD-1 blockers.
  • the present application provides a method of treating head and neck squamous cell carcinoma, comprising administering ginsenoside and a PD-1 blocker to a subject in need thereof.
  • the ginsenoside is ginsenoside Rh2 or Rg3.
  • the PD-1 blocking agent is an anti-PD-1 antibody, preferably pembrolizumab.
  • the ginsenoside enhances the inhibitory effect of PD-1 blocker on head and neck squamous cell carcinoma.
  • the ginsenoside enhances immune cell infiltration levels in tumor tissue.
  • the ginsenoside and PD-1 blocking agent enhance the killing effect of lymphocytes on tumor cells.
  • the ginsenoside in the medicine is in oral dosage form, and the PD-1 blocker is in injection form.
  • the clinical dosage of ginsenosides in the medicine is 1.5-2.0 mg/kg.
  • the medicine also includes other medicines used for the treatment or auxiliary treatment of head and neck squamous cell carcinoma.
  • the medicine used for the treatment or auxiliary treatment of head and neck squamous cell carcinoma is Ganoderma lucidum polysaccharide and/or astragalus polysaccharide.
  • the medicine also contains pharmaceutically acceptable excipients.
  • PD-1 refers to Programmed death-1 and programmed cell death receptor 1; these names can be used interchangeably to express the same meaning.
  • the ginsenosides in this application can use various types that have been identified and studied, preferably ginsenoside Rh2; ginsenoside Rh2 is the metabolite of ginsenoside Rg3, and the pharmacological activities of the two should be similar, so ginsenoside Rg3 should also be able to interact with PD
  • ginsenoside Rg3 should also be able to interact with PD
  • the combined use of -1 blockers can achieve similar effects to ginsenoside Rh2.
  • the ginsenosides and PD-1 blockers in the medicine of the present application can be prepared in the same pharmaceutical composition, or in different pharmaceutical compositions and used together.
  • ginsenosides and PD-1 blockers include but are not limited to oral preparations, such as tablets, capsules, oral liquids; injections, such as water injections, powder injections, etc. Those skilled in the art can select dosage forms based on common pharmaceutical knowledge and available dosage forms of existing PD-1 blockers.
  • pharmaceutically acceptable excipients that can be used in the pharmaceutical composition of the present application include but are not limited to solvents, cosolvents, surfactants, pH adjusters, osmotic pressure regulators, stabilizers, dispersants, Fillers, adhesives, coating agents, capsule shells, flavoring agents, etc.
  • Other drugs used for the treatment or adjuvant treatment of head and neck squamous cell carcinoma include various known and researched Chinese and Western drugs, such as Ganoderma lucidum polysaccharide, astragalus polysaccharide and other natural products with immune-enhancing effects, other chemotherapy drugs, targeted drugs, etc.
  • ginsenoside Rh2 and PD-1 blockers can enhance the inhibitory effect of PD-1 blockers on head and neck squamous cell carcinoma, enhance the infiltration level of immune cells in tumor tissues, and enhance the killing effect of lymphocytes on tumor cells. , providing a new way to treat head and neck cancer, a difficult cancer.
  • Figure 1 shows the effects of nine ginsenoside monomers on the proliferation of tongue squamous cell carcinoma Cal-27 cells
  • Figure 2 is a diagram showing the effect of ginsenoside Rh2 combined with anti-PD-1 antibody on tumor cells. Tumor cells are labeled with red fluorescent reagent, so changes in the number of tumor cells are expressed as fluorescence area;
  • Figure 3 shows the effects of ginsenoside Rh2 and anti-PD-1 antibodies on the number of tumor cells.
  • Cal-27 cells and PBMC were co-cultured with or without ginsenoside Rh2 or anti-PD-1 antibody respectively.
  • the concentrations of ginsenoside Rh2 were 1 ⁇ M, 5 ⁇ M and 10 ⁇ M respectively, and the concentration of anti-PD-1 antibody was 5 ⁇ g/mL. **P ⁇ 0.01, ****P ⁇ 0.0001;
  • Figure 4 is a diagram showing the effect of ginsenoside Rg3 combined with anti-PD-1 antibody on tumor cells. Tumor cells are labeled with red fluorescent reagent, so changes in the number of tumor cells are expressed as fluorescence area;
  • Figure 5 shows the effects of ginsenoside Rg3 and anti-PD-1 antibodies on the number of tumor cells.
  • Cal-27 cells and PBMC were co-cultured with or without ginsenoside Rg3 or anti-PD-1 antibody respectively.
  • the concentrations of ginsenoside Rg3 were 1 ⁇ M, 5 ⁇ M and 10 ⁇ M respectively, and the concentration of anti-PD-1 antibody was 5 ⁇ g/mL.
  • Figure 6 shows the effects of ginsenoside Rh2 and anti-PD-1 antibodies on tumor growth.
  • A Effects of ginsenoside Rh2 and anti-PD-1 antibody on tumor volume in mice.
  • B Effects of ginsenoside Rh2 and anti-PD-1 antibody on tumor weight in mice.
  • the dose of ginsenoside Rh2 was 15 mg/kg, and the dose of anti-PD-1 antibody was 200 ⁇ g/mouse.
  • Figure 7 shows the effects of ginsenoside Rh2 and anti-PD-1 antibody on immune cell infiltration in mouse tumor tissues.
  • A (D) The effect of ginsenoside Rh2 and anti-PD-1 antibody on T cells;
  • B (E) The effect of ginsenoside Rh2 and anti-PD-1 antibody on CD8 + T cells;
  • C (F) Effects of ginsenoside Rh2 and anti-PD-1 antibodies on B cell activation. *P ⁇ 0.05, **P ⁇ 0.01.
  • the anti-PD-1 antibody used in the following experiments is pembrolizumab; the tumor cells are Cal-27 cells or SCC-7 cells; the lymphocytes are lymphocytes induced by PBMC stimulated by PHA.
  • Example 1 Effect of 9 kinds of ginsenoside monomers on the proliferation of tongue squamous cell carcinoma Cal-27 cells
  • ginsenosides Rh1, Rc, Re, Rb3, Rg1 and Rb1 have a concentration-dependent inhibitory effect on Cal-27 cells.
  • the inhibitory effect is weak at low concentrations and strong at high concentrations.
  • the IC50 is all in Around 100 ⁇ M.
  • ginsenosides CK, Rh2 and Rg3 have the most significant inhibitory effects on Cal-27 cells, and have good inhibitory effects at low concentrations.
  • Example 2 Effect of combined use of ginsenoside Rh2/Rg3 and anti-PD-1 antibody on lymphocyte killing in vitro
  • ginsenoside Rh2 combined with anti-PD-1 antibody at 5 ⁇ M and 10 ⁇ M can further enhance the killing effect of lymphocytes, and the results are statistically significant (P ⁇ 0.05).
  • the anti-PD-1 antibody can significantly promote the killing effect of lymphocytes; compared with the anti-PD-1 antibody alone, ginsenoside Rg3 at 5 ⁇ M combined with the anti-PD-1 antibody Combined use can significantly enhance the killing effect of lymphocytes.
  • mice SPF grade C57 mice, 6 weeks old, female, were purchased from Beijing Vitong Lever Laboratory Animal Company. They were reared in the Animal Center of the Institute of Medicinal Plants, Chinese Academy of Medical Sciences. The experimental facilities comply with barrier environmental standards, with the temperature maintained at 20-26°C, the relative humidity at 40-70%, and light and dark alternating for 12 hours each. Mice were raised in standard boxes, with 5 mice per cage. During the raising process, the animals were allowed to eat and move freely.
  • mice were randomly divided into four groups: model control group, ginsenoside Rh2 group (15 mg/kg), anti-PD-1 antibody group (200 ⁇ g/mouse), and ginsenoside Rh2 combined with anti-PD-1 antibody group.
  • the administration time and volume were as follows: ginsenoside Rh2 was administered intragastrically 5 days before vaccination; anti-PD-1 antibody was administered intraperitoneally on days 3, 6, 9, and 12 after vaccination.
  • the growth status of the transplanted tumors was monitored every day, and the effects of tumor growth and drug treatment on the normal behavior and weight of the mice were observed. Throughout the experiment, the tumor volume of the mice was measured twice weekly.
  • mice's eyeballs were removed to collect blood, and the tumor tissue was peeled off.
  • the tumor tissue was divided into two parts, one part was quickly frozen in liquid nitrogen and then transferred to a -80°C refrigerator for storage, and the other part was stored in PBS solution for flow cytometry detection.
  • Mouse tumor samples were cut into pieces with sterile scissors, ground gently with a syringe stopper, and filtered through a 40 ⁇ m filter to prepare a single cell suspension. Transfer the cell suspension to a new centrifuge tube, add PBS solution, discard the supernatant after centrifugation, wash with PBS and centrifuge again. Add PBS to resuspend, take 100 ⁇ L into the flow tube, add the corresponding flow cytometry antibody, incubate and stain for 20 minutes, and then perform on-machine detection.
  • Ginsenoside Rh2 can enhance the inhibitory effect of anti-PD-1 antibodies on head and neck squamous cell carcinoma
  • the tumor volume of the mice in the model control group continued to increase over time.
  • the use of ginsenoside Rh2 alone could significantly reduce the tumor size of the mice.
  • the tumor volume of the mice using anti-PD-1 antibody alone decreased slightly.
  • the combination of ginsenoside Rh2 and anti-PD-1 antibody can further reduce the tumor volume compared with single use, and the difference is statistically significant (P ⁇ 0.05, Figure 6A).
  • the tumor tissue was peeled off and weighed.
  • the effects of ginsenoside Rh2 and anti-PD-1 antibody on mouse tumor weight were similar to the results of tumor volume (Figure 6B).
  • the above results show that ginsenoside Rh2 can significantly promote the inhibitory effect of anti-PD-1 antibodies on head and neck squamous cell carcinoma, and the combination of the two has a synergistic effect.
  • Ginsenoside Rh2 can enhance the level of immune cell infiltration in mouse tumor tissues

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Endocrinology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

La présente demande concerne l'utilisation d'un ginsénoside en combinaison avec un bloqueur de PD-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou, ainsi qu'une composition pharmaceutique correspondante. Selon la présente demande, l'utilisation combinée du ginsénoside Rg3 et d'un métabolite Rh2 de celui-ci avec le bloqueur PD-1 peut améliorer l'effet inhibiteur du bloqueur PD-1 sur le carcinome à cellules squameuses de la tête et du cou, améliorer le niveau d'infiltration de cellules immunitaires dans des tissus tumoraux, et améliorer l'effet destructeur de lymphocytes sur des cellules tumorales, fournissant une nouvelle option de médication pour le traitement du carcinome à cellules squameuses de la tête et du cou. La présente demande présente de larges perspectives d'application médicale.
PCT/CN2023/075142 2022-07-08 2023-02-09 Utilisation de ginsénoside en combinaison avec un bloqueur de pd-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou WO2024007583A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202210806755.5A CN115300624A (zh) 2022-07-08 2022-07-08 人参皂苷联合pd-1阻断剂在制备抗头颈鳞癌药物中的应用
CN202210806755.5 2022-07-08

Publications (1)

Publication Number Publication Date
WO2024007583A1 true WO2024007583A1 (fr) 2024-01-11

Family

ID=83856556

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2023/075142 WO2024007583A1 (fr) 2022-07-08 2023-02-09 Utilisation de ginsénoside en combinaison avec un bloqueur de pd-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou

Country Status (2)

Country Link
CN (1) CN115300624A (fr)
WO (1) WO2024007583A1 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115300624A (zh) * 2022-07-08 2022-11-08 中国医学科学院药用植物研究所 人参皂苷联合pd-1阻断剂在制备抗头颈鳞癌药物中的应用

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019028012A2 (fr) * 2017-07-31 2019-02-07 Dana-Farber Cancer Institute, Inc. Procédés d'utilisation de pembrolizumab et de trébananib
CN110404067A (zh) * 2019-09-06 2019-11-05 锦州医科大学 一种治疗结直肠癌的药物组合物
US20210023104A1 (en) * 2018-04-17 2021-01-28 Sheau-Long Lee Use of ginsenoside m1 for manufacturing medicament for treating oral cancer
US20220202818A1 (en) * 2019-04-18 2022-06-30 The Regents Of The University Of Michigan Combination with checkpoint inhibitors to treat cancer
CN115300624A (zh) * 2022-07-08 2022-11-08 中国医学科学院药用植物研究所 人参皂苷联合pd-1阻断剂在制备抗头颈鳞癌药物中的应用

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019028012A2 (fr) * 2017-07-31 2019-02-07 Dana-Farber Cancer Institute, Inc. Procédés d'utilisation de pembrolizumab et de trébananib
US20210023104A1 (en) * 2018-04-17 2021-01-28 Sheau-Long Lee Use of ginsenoside m1 for manufacturing medicament for treating oral cancer
US20220202818A1 (en) * 2019-04-18 2022-06-30 The Regents Of The University Of Michigan Combination with checkpoint inhibitors to treat cancer
CN110404067A (zh) * 2019-09-06 2019-11-05 锦州医科大学 一种治疗结直肠癌的药物组合物
CN115300624A (zh) * 2022-07-08 2022-11-08 中国医学科学院药用植物研究所 人参皂苷联合pd-1阻断剂在制备抗头颈鳞癌药物中的应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
CHENG GONG, LI LIANG-BO;LIAO YONG;TAN JUN-WU;CAO XUE-QIU: "Clinical trial of ginsenoside Rh2 combined with concurrent radiotherapy and chemotherapy in the treatment of patients with nasopharyngeal carcinoma", THE CHINESE JOURNAL OF CLINICAL PHARMACOLOGY, vol. 33, no. 23, 17 December 2017 (2017-12-17), pages 2449 - 2451, XP093126648 *
TAYLOR MATTHEW H., BETTS COURTNEY B., MALONEY LAUREN, NADLER ERIC, ALGAZI ALAIN, GUARINO MICHAEL J., NEMUNAITIS JOHN, JIMENO ANTON: "Safety and Efficacy of Pembrolizumab in Combination with Acalabrutinib in Advanced Head and Neck Squamous Cell Carcinoma: Phase 2 Proof-of-Concept Study", CLINICAL CANCER RESEARCH, ASSOCIATION FOR CANCER RESEARCH, US, vol. 28, no. 5, 1 March 2022 (2022-03-01), US, pages 903 - 914, XP093126386, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-21-2547 *
YAJUAN XU, JIN ZHIWEI; LIU LILI, LIU WENSHU: "Ginsenoside Rh2 Induces Apoptosis of Drug-Resistant Cell of Oral Squamous Cell Carcinoma", CHINESE JOURNAL OF GERONTOLOGY, vol. 37, no. 16, 25 August 2017 (2017-08-25), pages 3956 - 3958, XP093126645 *

Also Published As

Publication number Publication date
CN115300624A (zh) 2022-11-08

Similar Documents

Publication Publication Date Title
CN110381938A (zh) 减少中性粒细胞缺乏症的方法
US9005678B1 (en) Pharmaceutical composition for treating cancer and use thereof
CN105963637B (zh) 隐丹参酮联合姜黄素在制备肿瘤治疗药物中的应用
WO2024007583A1 (fr) Utilisation de ginsénoside en combinaison avec un bloqueur de pd-1 dans la préparation d'un médicament contre le carcinome à cellules squameuses de la tête et du cou
JP2018517759A (ja) カルボプラチンを含む組成物及び用途
JP4944380B2 (ja) 抗腫瘍活性および抗毒活性のある抽出物
WO2015192758A1 (fr) Application pharmaceutique anti-tumorale de composés de saponine de triterpène pentacyclique de racine de szechuan melandium
CN105796638B (zh) 冬凌草甲素联合隐丹参酮在制备白血病治疗药物中的应用
CN108553495A (zh) 一种抗肿瘤的中药组合物、活性成分组合物及其用途和制剂
US20230149347A1 (en) CXCR4/CXCR7 Blockade and Treatment of Human Papilloma Virus-Associated Disease
CN111888370A (zh) 一种虾青素和人参皂苷Rg3联合组合物制备抗肝癌的药物
JP7017011B2 (ja) マイコバクテリウムパラゴルドネの抗癌免疫治療法用途
CN106163515A (zh) 抗癌剂和副作用减轻剂
US9943560B2 (en) Medical compositions containing liquorice extracts with synergistic effect
CN111514290B (zh) 一种葫芦素组合物及其用途
CN105833173B (zh) 冬凌草甲素联合姜黄素在制备白血病治疗药物中的应用
CN111700900A (zh) 一种天然免疫活化剂、til细胞促进剂及其应用
CN104523698B (zh) 常春藤皂苷元在制备抗子宫内膜癌细胞hec-1肿瘤药物中的应用
CN106714807A (zh) 喜树碱衍生物在制备用于治疗多发性骨髓瘤的药物中的用途
CN102440994A (zh) 灵芝酸g在肿瘤治疗中作为免疫增效剂和超抗原依赖的治疗药物的应用
CN114748630B (zh) 具有改善功效的铂类抗癌药物组合物及其用途
CN114159533B (zh) 一种治疗多重耐药细菌感染的中药组合物及其应用
CN111202818B (zh) 一种中药组合物及其制备方法和应用
CN108743796B (zh) 一种治疗肺癌的中药组合物及其应用
CN110947004B (zh) 药物组合物及其应用、无菌容器和试剂盒

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23834368

Country of ref document: EP

Kind code of ref document: A1